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This is the first of a two part series on atherosclerosis and will explain:

What atherosclerosis actually is (and what it is not)

Why it’s important, and

What causes it

We will lay down a basic framework that will help you form a mental model so that next week we can cover what you need to know in order to prevent or reverse atherosclerosis.

What is atherosclerosis?Atherosclerosis - commonly known as “ hardening of the arteries” refers to a disease process that causes damage to the arteries resulting in narrowing, blockage, occlusion and even rupture.Atherosclerosis is the underlying cause of most cardiovascular disease (CVD) - including heart disease and stroke.

Every 7 minutes a Canadian dies from heart disease or stroke

Heart disease and stroke is the number one cause of death in Canada - accounting for 46% of all deaths; and also represent the single biggest cause of disability adjusted life years lost (DALY’s) - a measure of “lost healthy years”.

80% of premature heart disease and stroke can be prevented through healthy lifestyle choices

Only 1 in 10 Canadians are in ideal heart health

Over 90% of Canadians have at least one risk factor

Atherosclerosis is both very common and very preventable.Our view is that the key to prevention comes from really understanding how atherosclerosis develops. This involves getting past some common misconceptions that have resulted from an oversimplification of the disease through the two dominant conceptual models used to explain atherosclerosis:

Clogged pipes (arteries) are the problem; and

Fat Clogs Arteries

The issue with each of these models is that they overlook some key facts and observations:

Most cardiac events occur where there is minimal or moderate narrowing

The cholesterol (fat) found in atherosclerotic lesions is not from the diet but produced by the liver.

Most cardiac events occur in people with normal cholesterol levels

Before we go further here - let's back up and better understand the disease process:

The now dysfunctional endothelial cells, also send out molecular messenger signals such as IL-6 and TNF-alpha which trigger liver cells to increase production of the inflammatory molecule C-reactive protein.

The monocytes that attach to the endothelium, enter the subendothelial space, the intima and differentiate in macrophages - a specialized immune cell designed to inges toxic substances

In this case the macrophages essentially eat up the oxidized LDL particles, and as these cells become full, stuffed with cholesterol, they are aptly named “foam cells”

Multiple foam cells coalesce together to form a “fatty streak” in the artery wall - this is the hallmark of early atherosclerosis

Fatty streaks are almost ubiquitous and have even been found in utero! This is the very earliest stage of atherosclerosis and almost all of us have disease at this stage.

High Density Lipoprotein (HDL) - another lipid transport molecule - can enter the subendothelial space and take cholesterol from the foam cells, and subsequently distribute the cholesterol to other tissues in the body.

Foam cells that do not get relieved of the cholesterol burden - produce a variety of molecules including angiotensin II, metalloproteinases, collagenases, elastases, and other proteins - all of which can further undermine the integrity and function of the endothelium

At this point, the damage really begins. The endothelial damage signals smooth muscle cells to the damaged area where they secrete a matrix to heal the arterial wall. This matrix forms a fibrous cap that now can intrude into the lumen of the artery.

The atherosclerotic plaque, so formed, can become very large and can impede arterial blood flow to the extent in the heart that the muscle the artery serves can become starved of oxygen. This narrowing and decreased blood flow, results in the the exertional chest discomfort known as angina.

The metalloproteinases and collagenases produced by foam cells can also weaken the fibrous cap resulting in rupture of the plaque

This process can occur rapidly and result in complete occlusion of the artery - even when the initial lesion did not produce significant narrowing - this occlusion occurring in a coronary artery is known as a myocardial infarction (MI) or more commonly referred to as a heart attack.

To summarize, atherosclerosis is caused by an inflammatory response to oxidized lipoproteins within the artery wall. There are three main ingredients that trigger a lesion:

Oxidation of the sub-endothelial LDL-particles, causes inflammation resulting in

Dysfunctional endothelial cells that trigger further immune response.

The developing process can be mitigated in its earliest phases by HDL-particles that take away the sub-endothelial cholesterol - even after it is taken up by the foam cells.

Evidence shows that the risk of atherosclerosis increases with increasing concentrations of LDL-particles in linear fashion - note this LDL-particle numbers, not LDL-cholesterol concentration. (while LDL-C and LDL-p are generally concordant, ie. they increase and decrease together, this is not always true - especially when insulin resistance is present). LDL-cholesterol is what is commonly reported on the standard lipid panel. A better test to understand your risk is the ApoB100 protein- which gives you the number of LDL-particles as each LDL-particle has one ApoB100

It must be stressed that LDL-P easily enter and exit the sub-endothelial space all the time - it is the oxidation of LDL-P that is key step in initiating atherosclerosis. Only oxidized LDP-P is taken up by macrophages and foam cells.

Another key point is that the process that leads to an atherosclerotic lesion is systemic - so just identifying and treating lesions that cause blockage (ie. plumbing model) does not sufficiently decrease risk as there may be other non-obstructive lesions that can rupture and cause acute occlusion.

So in essence, with atherosclerosis we have a reinforcing cycle of:

Endothelial dysfunction leading to the

Oxidation and retention of lipoproteins in the subendothelial space leading to

Inflammation that results in further

Endothelial dysfunction

The take-home points to remember are:

atherosclerosis is the number cause of death in Canada

80% of premature deaths from atherosclerosis are preventable

the disease process is systemic and the conditions that lead to atherosclerosis affect all arteries

because it is systemic - a systemic approach to prevention, treatment, and reversal of atherosclerosis is required

atherosclerosis takes a long time to become symptomatic and most heart attacks occur in people who have had no prior symptoms

atherosclerosis is caused by a combination of endothelial dysfunction that allows for the oxidation of LDL cholesterol in the lining of the artery, resulting in an inflammatory response that triggers further endothelial dysfunction.

understanding an individual's

lipoprotein status

inflammation levels

endothelial function

are essential in order to develop a coherent reduction strategy.

Next week - we will apply this framework to explain the Wellness Garage prevention and risk reduction strategy for atherosclerosis.

At Wellness Garage - we can help you understand and take control of your health. Our comprehensive medical, fitness, nutritional and behavioral assessments give you baseline from which to measure your progress. Our coaching helps you improve your behaviors, one habit at a time.

50% of Americans have high blood pressure according to the new guidelines from American College of Cardiology and the American Heart Association.

Lost in the debate about whether this makes sense to label so many people with a disease was the recognition that normal blood pressure is now defined as 120/80 and the acknowledgement that the risks from blood pressure increase progressively, and linearly from levels as low as 115/75 in people from 40 to 89 years of age.

For every increase of 20 mmHg systolic and 10 mmHg diastolic there is a doubling of mortality from both heart disease and stroke.

Here is the Wellness Garage strategy for high blood pressure:

1. Know your blood pressure:

be confidant that your blood pressure is normal.

If you get high readings in the doctor's office - get an automated BP cuff for home.

If your doctor is not using an automated cuff - ask her why? New guidelines are clear that physicians should be using automated cuffs.

If your arm is large be sure to have a large cuff - make sure the doctor uses a large cuff.

2. Know whether you have insulin resistance:

if your blood sugars are abnormal then you already have insulin resistance

if your blood sugars are normal and you have abnormal lipids (high triglycerides and low HDL) and a waist size of >102 cm (40 in) in men or >88 cm (35 in) in women - you likely have a degree of insulin resistance

insulin resistance disrupts one of the key hormonal systems regulating BP - the Renin-Angiotensin system (RAS)

if you have insulin resistance - decreasing carbohydrates through a low carb, whole food approach makes the most sense - see #3

if you are diabetic these changes should be medically supervised

3. Get moving - exercise is key

aerobic exercise has been shown to lower BP 5-7 mmHg

resistance exercise lowers BP 2-3 mmHg

these effects rival first line drug therapy and lower risk by themselves 20-30%

recent evidence shows that exercise is superior to drug therapy in preventing death from stroke and is equal to drugs in prevention of heart disease mortality.

studies show that in overweight or obese people a weight loss of 8kg will lower BP by 8.5 mmHg systolic and 6.5 mmHg

these effects rival drug therapy and are though to be independent of exercise

5. Salt - stop eating packaged food and decrease how much you eat out - see #3

for years the linkage between salt (sodium) intake and elevated BP has been clear and part of the established recommendations for preventing and treating hypertension

more recently this has been challenged on at least two fronts

there is great variability between people on the basis of race, gender, age and dietary factors - resulting in the observation that some people at some times are salt sensitive - meaning that their BP increases with salt intake.

there is little convincing evidence to link decreased salt intake over time with better health outcomes.

our advice is to start by eliminating the real culprits in the high salt world we live in - restaurants (especially fast food) and packaged food. Eating real whole foods that you prepare yourself will result in a significant reduction of salt intake and will help with #3.

6. Reduce Stress - meditate

there is growing empirical evidence that the exposure to chronic psychological stress leads to the development of high blood pressure

while many relaxation therapies are recommended and are effective in reducing stress, so far only meditation has been shown to reduce stress and lower blood pressures

learning to meditate has never been easier with the introduction of apps like Headspace and Calm - finding 10-15 min per day to meditate will reduce stress and help you improve your blood pressure

7. Sleep - develop a great sleep routine

depriving people of sleep in the short-term clearly increases blood pressure

chronic sleep deprivation of < 5hrs per night doubles the risk of hypertension, while

insomnia and restless leg syndrome have also been shown to increase incidence of high blood pressure

if you snore regularly or stop breathing during the night -see you physician and get assessed for Obstructive Sleep Apnea

develop a great sleep routine - get 7-8 hrs of high quality sleep

This 7 step strategy will allow you to take control of your blood pressure and do everything you can to either avoid medication or take as little as possible.

Backgrounder on Hypertension:

What is it?

When your heart beats, blood is pushed through your arteries and veins. The pressure the blood exerts on the walls of the artery is appropriately called blood pressure (BP) - systolic BP represents the pressure during the heart's contraction phase, diastolic BP the pressure during the relaxation phase, and BP is recorded as systolic/diastolic. Blood pressure is controlled by two variables: the amount of blood pushed out of the left ventricle of the heart (cardiac output) and the resistance of the circulatory system to the flow of blood (peripheral resistance). This resistance is managed through complex mechanisms mediated by our autonomic nervous system that dilate or constrict our blood vessels. At the same time our blood volume is adjusted by our kidneys with the retention or excretion of salt and water.

Blood pressure, like all of our physiology is homeostatic - meaning that stability is generated through a balance or equilibrium of seemingly competing systems.

How is it defined?

Blood pressure is measured in mm of mercury (Hg). The American College of Cardiology and the American Heart Association recently released new guidelines (2017) that will increase the number of people diagnosed with hypertension to over 50% of the US population.

These guidelines reflect evidence that normalizing blood pressure to a target of 120 decreases risk significantly.

Why is it important?

Left uncontrolled high blood pressure can damage your arteries, increasing the risk of atherosclerosis, a disease where plaque builds up in the wall of your artery narrowing blood flow, and potentially blocking flow completely through plaque rupture or extreme narrowing and occlusion. Atherosclerosis has multiple outcomes depending on the arteries affected:

in the arteries of the heart: angina (chest pain) and myocardial infarction (MI or Heart Attack),

in the brain: stroke, from blockage or bleeding

in the kidneys: kidney failure

in the aorta (and other vessels) - ballooning (aneurysm) or rupture

Hypertension also can damage the heart, initially causing the heart muscle to expand and the heart to dilate (Left ventricular hypertrophy and dilatation) resulting in heart dysfunction and congestive heart failure

In addition to damaging the larger arteries of the kidney - hypertension damages the glomeruli - the small blood vessel clusters that are the filtration units of the kidney; and as a result of the effect on both the large and small arteries, hypertension is one of the most common causes of kidney failure.

These same effects to small blood vessels also damage the blood vessels of the retina (retionopathy) resulting in vision loss and even blindness

What causes it?

Most hypertension is from causes unknown and is characterized as primary hypertension.

The risk factors for primary high blood pressure are:

family history

age

race

obesity

physical inactivity

kidney dysfunction

high sodium diets

excessive alcohol

Causes of secondary hypertension

Medications - oral contraceptives, anti-inflammatories, antidepressants, decongestants being among the most common

Drugs - cocaine, metamphetamine

Kidney failure

Endocrine disorders - both hypothyroid and hyperthyroidism and a multitude of other more rare.

During this time, the rate of cardiovascular disease (CVD) has decreased to approximately 1/3 of their 1960's levels. While there are many factors (decline in smoking, better control of hypertension, use of statin drugs, and the timely use of blood thinners in acute myocardial infarctions) some cardiologists point to this decline as proof that the nutritional recommendations made in the late 1970's to reduce fat intake and specifically target saturated fat is a big part of this success.

"Is saturated fat bad for you?", remains one of the most contentious and confusing questions in medicine today.

I would like to unpack this for you, give you some background, and lay out a practical non-dogmatic approach for you to follow personally.

Background - The Diet:Heart Hypothesis"In the 1960's several observations were combined to form the diet:heart hypothesis which stated:Lowering cholesterol by replacing saturated fat with poly unsaturated fat (PUFA) from vegetable oil would:

diminish the deposition of cholesterol in the arterial wall,

slow progression of atherosclerosis,

reduce cardiovascular disease and

improve survival

This hypothesis, which has been the dominant paradigm for cardiology over the past 40 years was based on:

evidence from randomized controlled studies that showed replacement of saturated fat in the diet with PUFA from vegetable oil lowers total cholesterol and LDL cholesterol

The problem with the Diet:Heart hypothesis is that there has been no solid evidence to support the logical leap (A--->C)

​The original evidence to support the notion that decreasing saturated fat lowers coronary artery disease came from epidemiological studies in the 1960's that demonstrated a positive correlation between national levels of dietary fat consumption, and specifically saturated fat, and mortality from heart disease. The most famous (or infamous) study was performed by the legendary Ancel Keyes and was called the "7 Country Study".

This was an observational study based on fairly low-quality data: food diaries and public health records on cause of death. It also was not originally based on 7 countries - Keyes actually reviewed 22 countries - and when the whole dataset is reviewed the correlation, while present is far weaker. This has led to the suggestion that Keyes essentially cherry-picked the data to make the correlative conclusion stronger. He also refused to look at outlier cultures with very high saturated fat consumption and low rates of heart disease: Masai, Inuit etc.

By today's standards the 7 Country Study would be considered deeply flawed, and in fact recent observational studies have shown different results.

Most recently the PURE study, a large 18 country epidemiological cohort study that followed 135,335 people for an average of 7.4 years, demonstrated that high carbohydrate intake was associated with higher risk of total mortality whereas total fat and saturated fat intake were related to lower total mortality. Specifically saturated fat intake was not associated with increased risk of cardiovascular disease, heart attack, or cardiovascular disease mortality, and was actually associated with a decrease risk of stroke.

Of course, the challenge with these observational studies is that the best they can do is show correlation.

But correlation is not causation - my favorite example of this is the number of bathrooms one has correlates with net worth - the higher one's net worth the more bathrooms. Now if we confuse correlation with causation, we could erroneously conclude that having more bathrooms leads to higher net worth and could advocate that individuals should build themselves new bathrooms to increase their wealth!

The gold standard for proving causation is the randomized controlled study. This is where the diet:heart hypothesis really seems to fall apart.

One randomized controlled study that attempted to test the causal role of saturated fat in heart disease was the Minnesota Coronary Experiment (MCE).

Conducted from 1968 - 1973, MCE was the largest (9570 people) and most rigorously executed trial of the diet:heart hypothesis, and the only one to ever include post-mortem assessment of coronary, aortic and cerebrovascular atherosclerosis grade and infarct status.

The MCE followed over 9000 institutionalized people living in state mental institutions and nursing homes and randomly assigned them to two groups: one that maintained the standard diet high in saturated fat and the other group in which half of the calories from saturated fat were replaced with vegetable oil and corn oil margarine - high in the Omega 6 PUFA linoleic acid. Unlike observational studies, the MCE had detailed records of every meal administered to these subjects over a 56 month period.

This study probably could never be repeated as today's ethics boards would not approve experimenting on institutionalized patients without consent, and it would be impossible to control diet to the extent that they were able to in this trial.

So what were the findings:In keeping with the first part of the diet:heart hypothesis - replacing saturated fat with linoleic acid did lower cholesterol by an average of 14%, BUT this lowering of cholesterol DID NOT result in people living longer.

In fact, the lower the cholesterol the higher the rate of death (22% for every 0.75 mmol/L) and the vegetable oil group did not have fewer heart attacks or fewer atherosclerotic plaques.

So the MCE, the most rigorous trial ever done to test the diet:heart hypothesis essentially disproved the notion that decreasing saturated fat improves cardiovascular outcomes –it even suggested that increasing vegetable oil was associated with poor outcomes.

If this rigorous study was finished in 1973 and essentially disproved the diet:heart hypothesis, why did it not change the prevailing wisdom that saturated fat was bad?

It did not change minds because it was never published!

The investigators led by Ivan Frantz did not publish because the results were not what they expected and they felt that something must have been wrong with their data. When part of the study was published in 1989 it only reported that the substitution of saturated fats with vegetable oils did not reduce the risk of heart disease or death.

It was Ramsdem et al. who showed that when the whole data set was thoroughly reviewed that the MCE study results are counter to the diet:heart hypothesis and show that the replacement of saturated fat with vegetable oil increases coronary events and death.

In 2014, Chowdrury et al. reported a meta-analysis of 78 studies involving 650,000 people and concluded that there was no evidence that lowering saturated fat and increasing polyunsaturated fat intake decreases the risk of cardiovascular disease.

These studies in many ways disprove the diet:heart hypothesis as overly simplistic. Focusing on evidence that saturated fat elevates LDL cholesterol misses the fact that increasing saturated fat in the diet also increases HDL cholesterol and lowers triglycerides.

In recent years, the ratio of TG/HDL has been shown to be the best predictor of heart disease, superior to LDL cholesterol. Ratios that included HDL: Total Cholesterol/HDL and LDL/HDL also are stronger predictors that LDL alone.

Other evidence points to evidence that LDL particle size is likely more important than total LDL measurements. Individuals with small, dense LDL particles (Phenotype B) are at greater risk than individuals with larger, more buoyant LDL particles (Phenotype A).

Interestingly a high TG/HDL ratio correlates with the atherogenic Phenotype B – small, dense LDL particle size as well as insulin resistance.

From this we can see that the problem with the diet:heart hypothesis is that it ignores the effect of saturated fat on HDL and TG’s and assumes that the effect of LDL is all that there is to consider in terms of cardiovascular risk.

On the whole, this brings us to the answer to our question – Is saturated fat bad for you?

The overall evidence from these studies says probably not – but the real answer lies in your own individual response to increases or decreases in saturated fats, polyunsaturated fats, and carbohydrates. Specifically, what we track at Wellness Garage are your HDL, tryiglycerides and LDL particle number – in addition to markers of inflammation and insulin resistance, and with this data we have a far better idea of what effect your diet is having and what risk you face from cardiovascular disease.

Our view is not conventional wisdom – but we believe that it does represent the emerging consensus viewAt Wellness Garage our approach is personalized: